Fibrinogen is also called coagulation factor I, and is associated with forming of a fibrin clot in vivo. Fibrinogen becomes fibrin by the action of thrombin. The fibrin becomes firmly stabilized fibrin by the action of activated coagulation factor XIII, to form a fibrin clot. Fibrinogen is not only important for diagnosis and prognostication of hemorrhagic diseases, but also is an important index as a risk factor of thrombosis.
Examples of a fibrinogen measurement method include a thrombin time method (Clauss method), a salt precipitation method, immunonephelometry, and the like. In view of convenience and cost, the Clauss method is widespread. A thrombin-containing reagent and a kit for measuring fibrinogen, which are suitable for the Clauss method, are commercially available. The Clauss method is a method in which activity of fibrinogen is measured according to a time, in which fibrinogen is converted to fibrin by a predetermined amount of thrombin, depending on fibrinogen concentration. In the Clauss method, by generating a calibration curve based on a result of measuring of fibrinogen standard solution the concentration of which is known, an active concentration of fibrinogen in a blood specimen can be also obtained.
The Clauss method is preferably used because the Clauss method is applicable to an automatic blood coagulation measurement device. For example, Japanese Laid-open Patent Publication No. 2007-107889 discloses measuring a coagulation time by using a blood specimen analyzer, and obtaining a concentration of fibrinogen. In Japanese Laid-open Patent Publication No. 2007-107889, the concentration of fibrinogen is an active concentration of fibrinogen.
The active concentration of fibrinogen obtained by the Clauss method is a fibrinogen concentration obtained in the case of a function of the fibrinogen in a blood specimen being assumed to be normal. Therefore, when the active concentration is low, whether the cause is reduction of an amount of fibrinogen as protein (amount of antigen) or abnormal activity of the fibrinogen, needs to be separately confirmed. This is because a suspected disease is different depending on the cause of reduction of the active concentration. When the cause is reduction of an amount of antigen of fibrinogen, the suspected disease is fibrinogen deficiency or hypofibrinogenemia. When the cause is abnormal activity of fibrinogen, the suspected disease is fibrinogen disorder.
To date, an amount of antigen of fibrinogen is measured by immunological measurement such as a latex agglutination method. However, depending on facilities, although coagulation time is measured by the Clauss method, immunological measurement may not be performed. Therefore, means capable of obtaining information concerning an amount of antigen of fibrinogen, based on measurement of the coagulation time of a blood specimen having thrombin added thereto, is expected to be developed.
The inventors have found that a value of a parameter obtained by differentiating a coagulation waveform in a thrombin time method (Clauss method) and a total reaction time obtained from the coagulation waveform are well correlated with an amount of antigen of fibrinogen measured in a latex agglutination method, and have completed the present invention.